Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer.
Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.
Varambally
Sooryanarayana
S
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. soory@med.umich.edu
Laxman
Bharathi
B
Mehra
Rohit
R
Cao
Qi
Q
Dhanasekaran
Saravana M
SM
Tomlins
Scott A
SA
Granger
Jill
J
Vellaichamy
Adaikkalam
A
Sreekumar
Arun
A
Yu
Jianjun
J
Gu
Wenjuan
W
Shen
Ronglai
R
Ghosh
Debashis
D
Wright
Lorinda M
LM
Kladney
Raleigh D
RD
Kuefer
Rainer
R
Rubin
Mark A
MA
Fimmel
Claus J
CJ
Chinnaiyan
Arul M
AM
D014408:Biomarkers, Tumor / Q000032:analysis / Q000652:urine; D002460:Cell Line; D015331:Cohort Studies; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C410824:GOLM1 protein, human; D008565:Membrane Proteins; D017430:Prostate-Specific Antigen